The language and communication deficits that, in spite of the heterogeneous phenotype, by definition affect nearly autistic individuals to some degree, are perhaps the most devastating features of autism. We hypothesize that language impairments in autism are driven by early stage auditory cortical processing abnormalities and reduced connectivity between early auditory cortex and language areas. Indeed, several groups now show abnormal processing of auditory information in primary auditory cortex, and recent studies also point toward reduced functional connectivity in the autistic cortex. Another challenge of autism research is to establish links between functional response parameters, and anatomical and behavioral/clinical measures. The objectives of the proposed project are therefore (a) to characterize auditory processing deficits in autism, with an emphasis on local temporal dynamics in early auditory cortex and in language areas; (b) to study coherence of activity across brain regions that process auditory information, both within and across hemispheres, as a measure of functional connectivity; (c) to investigate the correlations between the extent of functional auditory processing impairments, and clinically determined language skills, as well as severity of the autism; (d) to coregister functional MEG data with multimodal anatomical MRI data in order to correlate tissue and functional abnormalities. Such levels of integration are necessary to establish quantitative biomarkers for early diagnosis, and to facilitate the design of specialized, well- targeted therapeutic interventions. To achieve these goals, auditory processing dynamics in healthy and autistic children ages 7 to 10 will be recorded using MEG, and mapped onto anatomical MRI data. Expected outcomes are (1) characterization of temporal dynamics of responses in auditory cortical areas in both populations (2) investigation of the hypothesis claiming reduced functional connectivity in autism with anatomical correlates, and (3) establishing whether cortical level impairments indeed lie at the origin of clinical observations of language and communication deficits that characterize autism, through correlations between functional and anatomical imaging measures, and behaviorally derived neurocognitive profiles. PUBLIC HEALTH RELEVANCE: Autism is a complex and devastating disorder which is diagnosed through a triad of behaviors and currently has full spectrum prevalence of about 1 in 175 children. In addition to affecting the individuals afflicted with the disorder, autism also affects not only the individual's family, but also the schools and communities, as the estimated cost of educating a child with autism in the public school system ranges from $50,000 to $80,000 per year, approximately 5 times the cost of educating a healthy child. This project aims to integrate functional and neuroanatomical studies of the neural substrates of autism, to better our understanding of the brain dysfunctions that cause autism, which in turn could contribute to the development of more effective treatments and, perhaps, approaches to allow for biological, rather than behavioral, and thus earlier, diagnosis. [unreadable] [unreadable] [unreadable]